Journal
ACS NANO
Volume 9, Issue 7, Pages 6918-6933Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.5b01042
Keywords
cancer vaccine; red blood cell; nanoparticles; dendritic cells; immunotherapy
Categories
Funding
- National Basic Research Program of China (973 Program) [2012CB932501]
- National Natural Science Foundation of China [81373360, 21474086]
- Ministry of Education of China [20120142120093]
- Fundamental Research Funds for the Central Universities [2014TS091]
- Chutian Scholar Award
- HUST
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Cancer immunotherapy is mainly focused on manipulating patient's own immune system to recognize and destroy cancer cells. Vaccine formulations based on nanotechnology have been developed to target delivery antigens to antigen presenting cells (APCs), especially dendritic cells (DCs) for efficiently induction of antigen specific T cells response. To enhance DC targeting and antigen presenting efficiency, we developed erythrocyte membrane-enveloped poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles for antigenic peptide (hgp100(25-33)) and toll-like receptor 4 agonist, monophosphoryl lipid (MPLA). A Mannose-inserted membrane structure was constructed to actively target APCs in the lymphatic organ, and redox-sensitive peptide-conjugated PLGA nanoparticles were fabricated which prone to cleave in the intracellular milieu. The nanovaccine demonstrated the retained protein content in erythrocyte and enhanced in vitro cell uptake. An antigen-depot effect was observed in the administration site with promoted retention in draining lymph nodes. Compared with other formulations after intradermal injection, the nanovaccine prolonged tumor-occurring time, inhibited tumor growth, and suppressed tumor metastasis in prophylactic, therapeutic, and metastatic melanoma models, respectively. Additionally, we revealed that nanovaccine effectively enhanced IFN-gamma secretion and CD8(+) T cell response. Taken together, these results demonstrated the great potential in applying an erythrocyte membrane-enveloped polymeric nanoplatform for an antigen delivery system in cancer immunotherapy.
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